crossing96/oncoscreening huggingface dataset:
Health-Related Quality of Life in a Real-World Cohort of Patients with Advanced Urothelial Carcinoma Treated with Immune Checkpoint Inhibitors.	INTRODUCTION: Health-related quality of life (HRQOL) has been reported in clinical trials of pembrolizumab and avelumab treatment of locally advanced or metastatic urothelial carcinoma. However, few studies have investigated the effect of immune checkpoint inhibitors (ICIs) on HRQOL in patients with urothelial carcinoma in a real-world setting. METHODS: We included 44 patients with advanced urothelial cancer who were treated with pembrolizumab or avelumab from January 2018 to November 2023. When patients visited our hospital for treatment, we evaluated their HRQOL using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 15-Palliative Care. We retrospectively reviewed the interview sheets. RESULTS: The median time to deterioration in global health status was 19.1 weeks. The mean scores of emotional functioning were improved in weeks 18 and 36 compared with baseline. The mean scores for fatigue and appetite loss were also improved in weeks 18 and 36. CONCLUSION: ICI treatment for advanced urothelial carcinoma did not worsen HRQOL over time in a real-world setting. Tolerability of ICIs for advanced urothelial carcinoma appears good in those who received long-term treatment.	bladder
PIN1 Prolyl Isomerase Promotes Initiation and Progression of Bladder Cancer through the SREBP2-Mediated Cholesterol Biosynthesis Pathway.	This study provides deeper insights into the regulatory role of the phospho-dependent prolyl isomerase PIN1 in bladder cancer. The identification of the link between PIN1 and SREBP2-mediated transcription and cholesterol biosynthesis offers the potential for developing novel therapeutic strategies for bladder cancer.	bladder
Spatial distribution and subtype-specific expression patterns of Nectin-4 in muscle-invasive bladder cancer.	OBJECTIVE: To investigate the expression patterns of Nectin-4, the target molecule of the antibody-drug conjugate enfortumab vedotin (EV), in relation to histological and molecular subtypes of urothelial bladder cancer (UBC). PATIENTS AND METHODS: We assessed the protein expression patterns of Nectin-4 in a spatially organised tissue microarray containing 1386 tissue cores from 314 consecutive patients with UBC who underwent radical cystectomy (2005-2018). Results were correlated with clinicopathological and follow-up data, as well as with different spatial locations (tumour central vs tumour-normal interface and primary tumour vs lymph node [LN] metastases). Additionally, we correlated Nectin-4 expression levels with histological and molecular subtypes. Finally, we assessed the value of Nectin-4 expression for predicting the efficacy of platinum therapy in the peri-operative setting. RESULTS: Nectin-4 expression was observed in 63% of primary tumours and 87% of LN metastases, with significantly higher levels in LNs. Of the histological subtypes, the micropapillary (58%) and pure urothelial histologies (30%) were associated with the highest Nectin-4 positivity, while the sarcomatoid (17%), squamous (15%) and small/cell-neuroendocrine (0%) subtypes exhibited the lowest. Nectin-4 immunopositivity rates were significantly higher in luminal (urothelial-like [42%] and genomically unstable [34%] Lund subtypes) compared to the basal (5%) or mesenchymal (0%) molecular subtypes. Higher Nectin-4 expression levels were associated with lower tumour stage but showed no association with overall survival. Finally, patients with low Nectin-4 expression tended to derive more benefit from platinum-based chemotherapy in both adjuvant and neoadjuvant settings (P < 0.001, P = 0.067). CONCLUSION: Our results revealed a low spatial heterogeneity of Nectin-4 expression within the primary tumour. In contrast, differential Nectin-4 expression was found in the context of histological and molecular subtypes. Nectin-4-expressing tumours may show varying sensitivity to both EV and platinum-based chemotherapy.	bladder
Immediate second resection versus restage transurethral resection of bladder tumor: A prospective randomized clinical trial (IMMERSE trial).	"BACKGROUND: The role of repeat transurethral resection of bladder tumor (TURBT) for the management of nonmuscle invasive bladder carcinoma is debated, especially when initial resections include detrusor muscle. This study compares immediate second resection (additional deep biopsies in the same session) with standard restage TURBT performed 2-6 weeks post-initial TURBT to determine adequacy in detrusor muscle sampling and compare the disease rate at restage TURBT in both groups. MATERIAL AND METHODS: A randomized trial was conducted at a tertiary care hospital, including patients aged ≥18 years undergoing TURBT with complete primary tumor resection. Cases were randomized into two groups i.e., 'standard TURBT' (complete tumor resection with a deep biopsy) and ""immediate second resection"" (complete tumor resection, deep biopsy and additional deep biopsies). The primary endpoint was the presence of detrusor muscle in biopsy specimens, analyzed by a single pathologist. Secondary endpoints included perioperative complications, residual/ recurrent tumors, and factors affecting these recurrences. RESULT: The study included 83 patients: 44 in the 'standard TURBT' group and 39 in the 'immediate second resection' group. The detrusor muscle was present in 66% of standard TURBT cases and 97% of immediate second resection cases, showing a statistically significant improvement (P = 0.000). Residual disease was found in 41% of restage TURBT patients in the standard group and 15% in the immediate second resection group, the majority being high-grade and T1 tumors (P = 0.028). There were no significant differences in tumor grade or perioperative complications between the groups. However, immediate second resection showed 18% higher detrusor muscle sampling rates than standard re-stage TURBT done at 2-6 weeks (P = 0.021). CONCLUSION: Immediate second resection at the time of initial TURBT significantly improves detrusor muscle sampling rates and decreases residual tumors at restage. Despite higher muscle sampling, a considerable proportion of patients still exhibited residual or recurrent tumors in both groups, emphasizing the need for improved detection and biopsy techniques during primary TURBT."	bladder
Study of urine-based mRNA biomarkers for early detection of nonmuscle invasive bladder cancer (NMIBC).	BACKGROUND AND OBJECTIVE: Research into new noninvasive diagnostic tools for bladder cancer (BCa) with superior sensitivity and specificity to cystoscopy and cytology is promising. The current study evaluated a diagnostic panel of tumor progression-related mRNAs in urine samples of NMIBC patients and controls. METHODS: This study carefully selected 129 participants, including 67 NMIBC patients, 31 hematuria patients due to nonmalignant urological disorders, and 31 healthy individuals. Subsequently, ten significantly dysregulated mRNAs were identified in the urine specimens of these participants using RT-qPCR. KEY FINDINGS: Expression levels of CA9, CDK1, CD24, TERT, CEP55, TOP2A, IQGAP3, UBE2C, and CRH in urine samples from NMIBC patients were higher than those in healthy individuals. Notably, CD24, TOP2A, IQGAP3, UBE2C, and CRH mRNA levels in NMIBC patients were significantly higher than in the hematuria group. In diagnosing low-grade from healthy and hematuria groups, analysis of the 5-gene profile yielded a sensitivity of 98 % and a specificity of 100 % and 90 %, respectively. For diagnosing high-grade tumors from healthy and hematuria groups, sensitivity was 96 % and 100 %, and specificity was 100 % and 83 %, respectively. CONCLUSIONS AND CLINICAL IMPLICATIONS: These results emphasize the potential application of urine mRNA profiling in the early diagnosis of NMIBC and provide new insights into the molecular mechanisms involved.	bladder
Enhanced Recovery After Surgery for patients undergoing radical cystectomy: Surgeons' perspectives and recommendations ten years after its implementation.	BACKGROUND AND OBJECTIVES: Enhanced Recovery After Surgery (ERAS) guidelines for Radical Cystectomy (RC) were published over ten years ago. Aim of this systematic review is to update ERAS recommendations for patients undergoing RC and to give an expert opinion on the relevance of each single ERAS item. METHODS: A systematic review was performed to identify the impact of each single ERAS item on RC outcomes. Embase and Medline (through Pubmed) were searched systematically. Relevant articles were selected and graded. For each ERAS item, a level of evidence was determined. An e-Delphi consensus was then performed amongst an international panel with renowned experience in RC to provide recommendations based on expert opinion. KEY FINDINGS AND LIMITATIONS: Preoperative medical optimization and avoiding bowel preparation are highly recommended. Robotic-assisted RC with intracorporeal urinary diversion is moderately recommended and can help in applying other ERAS items, such as early mobilization. Medical thromboprophylaxis should be administered and nasogastric tube should be removed at the end of surgery. Perioperative fluid restriction as well as opioid-sparing anesthesia protocols should be implemented. Generally, consensus was reached on most ERAS items, with the exception of epidural anesthesia (no consensus), resection site drainage (consensus against), and type of urinary drainage. Limitations include the lack of a multidisciplinary approach to the present consensus, giving however a highly specialized surgical opinion on ERAS. CONCLUSIONS: and clinical implications: The current study updates ERAS recommendations for patients undergoing RC and suggests application of ERAS by a panel of experts in the field.	bladder
A Comparison Between Intravesical Gemcitabine Plus Docetaxel and Intravesical Bacillus Calmette-Guérin in the Treatment of Nonmuscle Invasive Naive Urinary Bladder Cancer: A Systematic Review and Meta-analysis of Oncological Outcomes.	This study evaluated the efficacy, recurrence rates, and safety of intravesical gemcitabine plus docetaxel compared to standard Bacillus Calmette-Guérin (BCG) therapy for treating naïve non-muscle-invasive bladder cancer (NMIBC), with a focus on reducing recurrence and progression concerns associated with transurethral resection (TURBT). A systematic review and meta-analysis of three original studies were conducted, assessing recurrence rates and safety profiles. The meta-analysis revealed no heterogeneity in recurrence rates between the gemcitabine plus docetaxel and BCG groups, with an overall Odds Ratio for recurrence of 0.72 (95% CI: 0.36-1.47). Although the clinical recurrence rate was slightly lower in the gemcitabine plus docetaxel group, the difference was not statistically significant (Z = 0.89, P = 0.37). The gemcitabine plus docetaxel group experienced fewer severe side effects compared to the BCG group. Due to the limited number of studies available, further randomized trials are necessary to confirm the role of intravesical gemcitabine plus docetaxel in NMIBC management.	bladder
Gemcitabine and docetaxel for high-risk non-muscle-invasive bladder cancer: EuroGemDoce group results.	OBJECTIVE: To evaluate the oncological efficacy and safety of sequential intravesical gemcitabine/docetaxel (Gem/Doce) therapy in a European cohort of patients with high-risk and very-high-risk non-muscle-invasive bladder cancer (NMIBC) after previous Bacillus Calmette-Guérin (BCG) treatment. MATERIALS AND METHODS: Data were retrospectively collected from 95 patients with NMIBC, treated with Gem/Doce at 12 European centres between 2021 and 2024. Patients previously treated with BCG who had completed a full induction course and received at least one follow-up evaluation were included. One-year disease-free survival (DFS), high-grade DFS and progression-free survival (PFS) were estimated using Kaplan-Meier curves. Adverse events (AEs) were recorded through medical interviews. RESULTS: Of 75 patients, 63 (84%) were classified as having high-risk and 12 (16%) as having very-high-risk NMIBC. Over a median (interquartile range) follow-up of 9 (5-14) months, 20 patients (27%) relapsed and five (6.7%) underwent radical cystectomy. The 1-year DFS was 73% (95% confidence interval [CI] 62-86%), 1-year high-grade DFS was 79% (95% CI 68-91%) and 1-year PFS was 95% (95% CI 90-100%). AEs occurred in 34 patients (45%), with six (8.7%) experiencing severe AEs. Limitations of the study include the short follow-up and variability in both treatment dwelling times and dosage across centres. CONCLUSION: The intravesical Gem/Doce regimen demonstrated promising short-term oncological outcomes and was well tolerated in this cohort of patients with high- and very-high-risk NMIBC previously treated with BCG. Prospective studies and randomised trials are awaited to define the ideal candidates for Gem/Doce therapy and to standardise treatment protocols.	bladder
Detection of Human Bladder Epithelial Cancerous Cells with Atomic Force Microscopy and Machine Learning.	The development of noninvasive methods for bladder cancer identification remains a critical clinical need. Recent studies have shown that atomic force microscopy (AFM), combined with pattern recognition machine learning, can detect bladder cancer by analyzing cells extracted from urine. However, these promising findings were limited by a relatively small patient cohort, resulting in modest statistical significance. In this study, we corroborated the AFM technique's capability to identify bladder cancer cells with high accuracy using a controlled model system of genetically purified human bladder epithelial cell lines, comparing cancerous cells with nonmalignant controls. By processing AFM adhesion maps through machine learning algorithms, following previously established methods, we achieved an area under the ROC curve (AUC) of 0.97, with 91% accuracy in cancer cell identification. Furthermore, we enhanced cancer detection by incorporating multiple imaging channels recorded with AFM operating in Ringing mode, achieving an AUC of 0.99 and 93% accuracy. These results demonstrated strong statistical significance (p < 0.0001) in this well-defined model system. While this controlled study does not capture the biological variation present in clinical settings, it provides independent support for AFM-based detection methods and establishes a rigorous technical foundation for further clinical development of AFM imaging-based methods for bladder cancer detection.	bladder
Construction and validation of prognosis and treatment outcome models based on plasma membrane tension characteristics in bladder cancer.	BACKGROUND: Plasma membrane tension-related genes (MTRGs) are known to play a crucial role in tumor progression by influencing cell migration and adhesion. However, their specific mechanisms in bladder cancer (BLCA) remain unclear. METHODS: Transcriptomic, clinical and mutation data from BLCA patients were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Clusters associated with MTRGs were identified by consensus unsupervised cluster analysis. The genes of different clusters were analyzed by GO and KEGG gene enrichment analysis. Differentially expressed genes (DEGs) were screened from different clusters. Consensus cluster analysis of prognostic DEGs was performed to identify gene subtypes. Patients were then randomly divided into training and validation groups, and MTRG scores were constructed by logistic minimum absolute contraction and selection operator (LASSO) and Cox regression analysis. We assessed changes in clinical outcomes and immune-related factors between different patient groups. The single-cell RNA sequencing (scRNA-seq) dataset for BLCA was collected and analyzed from the Tumor Immune Single-cell Hub (TISCH) database. Biological functions were investigated using a series of experiments including quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), wound healing, transwell, etc. RESULTS: Our MTRG score is based on eight genes (HTRA1, GOLT1A, DCBLD2, UGT1A1, FOSL1, DSC2, IGFBP3 and TAC3). Higher scores were characterized by lower cancer stem cell (CSC) indices, as well as higher tumor microenvironment (TME) stromal and immune scores, suggesting that high scores were associated with poorer prognosis. In addition, some drugs such as cisplatin, paclitaxel, doxorubicin, and docetaxel exhibited lower IC50 values in the high MTRG score group. Functional experiments have demonstrated that downregulation of DCBLD2 affects tumor cell migration, but not proliferation. CONCLUSIONS: Our study sheds light on the prognostic significance of MTRGs within the TME and their correlation with immune infiltration patterns, ultimately impacting patient survival in BLCA. Notably, our findings highlight DCBLD2 as a promising candidate for targeted therapeutic interventions in the clinical management of BLCA.	bladder
Concomitant antihistamine administration is associated with improved survival outcomes in patients with locally advanced or metastatic urothelial carcinoma treated with atezolizumab. Analysis of individual participant data from IMvigor210 and IMvigor211.	OBJECTIVES: Survival outcomes of patients with metastatic urothelial carcinoma (mUC) are still suboptimal and strategies to enhance response to immune-oncology (IO) compounds are under scrutiny. In preclinical studies, it has been demonstrated that antihistamines may reverse macrophage immunosuppression, reactivate T cell cytotoxicity, and enhance the immunotherapy response. We aimed to evaluate the role of concomitant antihistamines administration on oncological outcomes among patients with mUC. MATERIALS AND METHODS: We relied on individual patient data from IMvigor210 (phase II single-arm trial on second line atezolizumab for mUC) and IMvigor211 trials (phase III randomized trial on second line atezolizumab vs chemotherapy for mUC). Among individuals treated with IO we identified patients who did and did not receive antihistamines. Multivariable Cox or competing-risks regression models were used to predict progression-free survival (PFS), overall survival (OS), and cancer-specific survival (CSS). The impact of antihistamines on the outcomes was assessed after adjusting for potential confounders. RESULTS: Among 896 patients with locally advanced or metastatic urothelial cancer who had progressed after first-line chemotherapy, 155 (17 %) received antihistamines during the delivery of IO. Patients receiving antihistamines had longer OS (Hazard Ratio [HR]:0.59; 95 % Confidence interval [CI]: 0.47-0.74; P < 0.001), PFS (HR:0.70; 95 %CI: 0.57-0.87; P = 0.001) and CSS [sHR:0.58; 95 %CI:0.45-0.75; P < 0.001)] relative to those who had not used antihistamine drugs. A sensitivity analysis, after the exclusion of patients who experienced adverse events and received antihistamines, yielded similar findings of prolonged CSS (sHR 0.78; 95 %CI: 0.59-0.98, P = 0.031) and OS (HR 0.71; 95 %CI: 0.52-0.94, P = 0.021). CONCLUSIONS: Concomitant antihistamines administration was associated with improved OS, CSS, and PFS in patients receiving atezolizumab as second line treatment for mUC. Further mechanistic and clinical investigation is warranted to elucidate the role of antihistamines in IO.	bladder
Environmental Exposures and Canine Bladder Cancer: A Case Control Study Using Silicone Passive Samplers.	Pet dogs offer valuable models for studying environmental impacts on human health due to shared environments and a shorter latency period for cancer development. We assessed environmental chemical exposures in a case-control study involving dogs at high risk of urothelial carcinoma, identified by a BRAF V595E mutation in urinary epithelial cells. Cases (n = 25) exhibited low-level BRAF mutations, while controls (n = 76) were matched dogs without the mutation. Each dog wore a silicone sampler for five continuous days to assess environmental exposures. Silicone samplers were analyzed using targeted and suspect screening (i.e., nontargeted) methods. Of 115 targeted chemicals, 39 were detected in >50% of samplers, with cases showing significantly higher levels (2-3×) of BDE-47, BDE-99, anthracene, and benzyl butyl phthalate (p < 0.05). Suspect screening identified that cases were exposed to more chemicals, often at higher exposure levels. For example, cases had significantly higher levels of 25 chemical features compared to controls (p < 0.05). This is the largest study to date to quantify such a wide breadth of contaminant exposure levels associated with canine urothelial carcinoma and the first to assess a population with subclinical disease, highlighting pet dogs as models to study environmental contributions to cancer risk, advancing both human and veterinary health.	bladder
The Role of SWI/SNF Complex in Bladder Cancer.	Bladder cancer originates from bladder tissues and is the ninth most common type of cancer worldwide. The SWI/SNF (SWItch/sucrose non- fermentable) complex plays a crucial role in regulating various biological processes, such as cell cycle control, DNA damage repair and transcription regulation. The purpose of this article is to examine the functional studies of the SWI/SNF complex in bladder cancer, highlighting new pathways for creating personalised treatment approaches for bladder cancer patients with mutations in the SWI/SNF complex. By acquiring a comprehensive understanding of the mechanisms of the SWI/SNF complex in bladder cancer, we can offer more precise and effective solutions to treat this disease.	bladder
[Enfortumab vedotin and pembrolizumab : Management of side effects during first line combined treatment for advanced or metastatic urothelial carcinoma].	The aim of this article is to raise awareness among healthcare providers about the adverse events (AEs) associated with the combined treatment with enfortumab vedotin and pembrolizumab. The differential diagnostic allocation of these AEs to the respective agents is discussed, overlaps between the side effect profiles of the two drugs are identified and strategies for an effective management of these AEs are presented. The recommendations are based on the currently valid prescription information for both drugs, the results of pivotal approval studies and the guidelines of recognized specialist organizations as well as the clinical experience of the authors.	bladder
Precision Oncology Approach for Urachal Carcinoma: A Clinical Case Report.	Urachal cancer (UrC) is a rare disease which is mostly diagnosed late due to symptoms caused by its local invasion to the urinary bladder. Given the lack of clinical trials and guideline recommendations for systemic treatment, a molecularly informed precision oncology approach is a viable option for UrC already in the early lines of systemic treatment. While single case experiences may provide valuable reference for later decision-making, well-documented clinical experience with off-label targeted treatments is limited to a few patients. Here, we report a case of a 31-year-old female UrC patient who underwent intensive therapy with three surgeries and five lines of systemic treatments, including chemo-, checkpoint inhibitor and tyrosine kinase inhibitor therapies. In addition, next-generation sequencing (NGS) analysis and an ex vivo drug-screening analysis were performed on patient-derived tumor cells and the results were implemented into the therapeutic decision-making. Finally, serum carcinoembryonic antigen (CEA) levels proved to be helpful for therapy monitoring during the whole follow-up period.	bladder